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- Persson, S., et al.
(författare)
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Burden of established cardiovascular disease in people with type 2 diabetes and matched controls : hospital-based care, days absent from work, costs, and mortality
- 2021
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 64:Suppl. 1, s. 17-17
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Established cardiovascular disease (eCVD) is associated with need for healthcare interventions, reduced work capacity and excess mortality. People with type 2 diabetes have increased risk and earlier onset of eCVD compared to people in general. The objective was to assess the burden of hospital-based care, days absent from work, associated costs, and excess mortality for people with type 2 diabetes with and without eCVD with comparison to matched controls.Materials and methods: The study used a Swedish retrospective data-base cross-linking longitudinal individual-level data (2007-2016) from national population-based health, social insurance, and socio-economic registers for 454,983 people with type 2 diabetes and their matched controls (5:1 on year of birth, sex, and region of residence). Statuse CVD (coronary artery disease, stroke, amputation, periphery vascular disease, non-fatal cardiac arrest, or related interventions) was derivedf rom retrospective data 1997-2006 and updated at change of status 2007-2016. Use of hospital-based care, days absent from work (calendar days) and mortality used data 2007-2016. Regression analysis accounting for individual-level clustering was used for comparison to controls and to attribute costs of hospital-based care and days absent from work to eCVD and to individual complications considering multimorbidity. Excess mortality adjusted for age, sex, and educational level was attributed to eCVD using Cox proportional hazards.Results: Thirty percent (n=136,135) of people with type 2 diabetes up to age 70 years were observed with eCVD≥1 observation year in 2007-2016 (women 24% n=43,847; men 34% n=92,288). The mean annual costs of hospital-based care for diabetes complications were EUR 2,758 (95% CI 2,729 to 2,787) of which EUR 2,461 (95% CI 2,432 to 2,490)were attributed to people with eCVD (89%). Main drivers of costs of hospital-based care for people withe CVD were acute myocardial infarction, angina pectoris, and stroke; but also end-stage renal disease (ESRD) andeye disease confirming that eCVD is associated with an increased burden from other complications. eCVD was a leading cause behind work absence for both diabetes and controls. People with type 2 diabetes <66 years had on average 146 days absent (95% CI 145-147) of which 68 days (47%) were attributed to eCVD. Controls had 106 days absent of which 63 days (59%) were attributed to eCVD. The annual cost of eCVD work absence was EUR 9,337 (95% CI 9,150 to9,523) per individual. The highest work absence was attributed to ESRD, stroke, and heart failure. Type 2 diabetes without eCVD did not differ from controls regarding mortality risk, but type 2 diabetes with eCVD had a four-fold risk of death hazard rate 4.13 (95% CI 4.10 to 4.18) adjusting for age, sex, and educational level.Conclusion: This study assessed the size of the burden of eCVD-status in people with type 2 diabetes in three measures: 1) eCVD was associated with excess mortality; 2) 9 out of 10 EUR spent on hospital-based care for diabetes complications; and 3) even higher costs of days absent from work in the long-run. Reducing the risks of living with eCVD and post-poning the onset of eCVD remain central goals to reduce the burden of type 2 diabetes on the individual and on society.
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| 43. |
- Shang, Ming-Mei, et al.
(författare)
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Lim domain binding 2 : a key driver of transendothelial migration of leukocytes and atherosclerosis
- 2014
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 34:9, s. 2068-2077
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Using a multi-tissue, genome-wide gene expression approach, we recently identified a gene module linked to the extent of human atherosclerosis. This atherosclerosis module was enriched with inherited risk for coronary and carotid artery disease (CAD) and overlapped with genes in the transendothelial migration of leukocyte (TEML) pathway. Among the atherosclerosis module genes, the transcription cofactor Lim domain binding 2 (LDB2) was the most connected in a CAD vascular wall regulatory gene network. Here, we used human genomics and atherosclerosis-prone mice to evaluate the possible role of LDB2 in TEML and atherosclerosis.APPROACH AND RESULTS: mRNA profiles generated from blood macrophages in patients with CAD were used to infer transcription factor regulatory gene networks; Ldlr(-/-)Apob(100/100) mice were used to study the effects of Ldb2 deficiency on TEML activity and atherogenesis. LDB2 was the most connected gene in a transcription factor regulatory network inferred from TEML and atherosclerosis module genes in CAD macrophages. In Ldlr(-/-)Apob(100/100) mice, loss of Ldb2 increased atherosclerotic lesion size ≈2-fold and decreased plaque stability. The exacerbated atherosclerosis was caused by increased TEML activity, as demonstrated in air-pouch and retinal vasculature models in vivo, by ex vivo perfusion of primary leukocytes, and by leukocyte migration in vitro. In THP1 cells, migration was increased by overexpression and decreased by small interfering RNA inhibition of LDB2. A functional LDB2 variant (rs10939673) was associated with the risk and extent of CAD across several cohorts.CONCLUSIONS: As a key driver of the TEML pathway in CAD macrophages, LDB2 is a novel candidate to target CAD by inhibiting the overall activity of TEML.
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- Skogsberg, Ulrika, et al.
(författare)
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Adult ABO-incompatible liver transplantation, using A and B donors
- 2006
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Ingår i: Xenotransplantation. - 0908-665X. ; 13:2, s. 154-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The longer waiting time for a liver graft in patients with blood group O makes it necessary to expand the donor pool for these patients. This applies in both urgent situations and for elective patients. We report on our experience with ABO-incompatible liver transplantation using A2 and B non-secretor donors here. PATIENTS AND METHODS: Between 1996 and 2005, 12 adult blood group O recipients (seven male/five female) received ABO-incompatible cadaveric liver grafts (10 A2 donors, two B non-secretor donors). The indications were either rapid deterioration of liver function or hepatocellular cancer, in blood group O recipients, where an ABO-identical/compatible graft was not available. Mean recipient age was 54+/-8 (mean+/-SD) yr. All pre-operative CDC crossmatches were negative. The initial immunosuppression was induction therapy with antithymocyte globulin (n = 3), interleukin 2 receptor antagonists (n = 3) or anti-CD20 antibody (rituximab) (n = 1), followed by a tacrolimus-based protocol. Three patients underwent plasmapheresis post-transplantation. Baseline biopsies were taken before or immediately after reperfusion of the graft and after grafting when clinically indicated. No pre-operative plasmapheresis, immunoadsorption or splenectomies were performed. RESULTS: Patient and graft survival was 10/12 (83%) and 8/12 (67%), respectively, with a 6.5-month median follow-up (range 10 days to 109 months). Two patients (B non-secretor grafts) died of multiorgan failure probably because of a poor condition before transplantation. Three patients were retransplanted. Causes of graft loss were bacterial arteritis (n = 1), death with a functioning graft (n = 1) and portal vein thrombosis (n = 2). In one of the patients with portal vein thrombosis, an anti-A titer increase occurred concomitantly, and ABO incompatibility as the cause of the thrombosis cannot be excluded. Seven acute rejections occurred in five patients and all were reversed by steroids or increased tacrolimus dosage. The pre-transplant anti-A titers tested against A1 red blood cells were 1 to 128 (NaCl technique) and 4 to 1024 (indirect antiglobulin technique, IAT); the maximum postoperative titers were 16 to 2048 (NaCl) and 256 to 32,000 (IAT). CONCLUSION: The favorable outcome of A2 to O grafting, with a patient survival of 10/10 and a graft survival of 8/10, makes it possible to also consider this blood group combination in non-urgent situations. The use of non-secretor donor grafts is interesting but has to be further documented. There was no hyperacute rejection or increased rate of rejection. Anti-A/B titer changes seem not to play a significant role in the monitoring of ABO-incompatible liver transplantation.
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